Mechanistical Insights into the Bioconjugation Reaction of Triazolinediones with Tyrosine

The Journal of Organic Chemistry
Dustin KaiserBernd Engels

Abstract

The bioconjugation at tyrosine residues using cyclic diazodicarboxamides, especially 4-substituted 3 H-1,2,4-triazole-3,5(4 H)-dione (PTAD), is a highly enabling synthetic reaction because it can be employed for orthogonal and site-selective (multi)functionalizations of native peptides and proteins. Despite its importance, the underlying mechanisms have not been thoroughly investigated. The reaction can proceed along four distinctive pathways: (i) the SEAr path, (ii) along a pericyclic group transfer pathway (a classical ene reaction), (iii) along a stepwise reaction path, or (iv) along an unusual higher order concerted pericyclic mechanism. The product mixtures obtained from reactions of PTAD with 2,4-unsubstituted phenolate support the SEAr mechanism, but it remains unclear if other mechanisms also take place. In the present work, the various mechanisms are compared using high-level quantum chemistry approaches for the model reaction of 4 H,3 H-1,2,4-triazole-3,5(4 H)-dione (HTAD) with p-cresol and p-cresolate. In a protic solvent (water), the barriers of the SEAr mechanism and the ene reaction are similar but still too high to explain the available experimental observations. This is only possible if the SEAr reaction of cres...Continue Reading

References

Sep 15, 1988·Physical Review A: General Physics·A D Becke
Jul 30, 2004·Organic Letters·Xin Lu
Mar 3, 2005·The Journal of Chemical Physics·Jamie M RintelmanMark S Gordon
Dec 29, 2007·The Journal of Organic Chemistry·Orlando Acevedo, Michael E Squillacote
Sep 26, 2008·Chemistry : a European Journal·Georgios C VougioukalakisMichael Orfanopoulos
Nov 8, 2008·Physical Chemistry Chemical Physics : PCCP·Jeng-Da Chai, Martin Head-Gordon
Feb 24, 2009·Clinica Chimica Acta; International Journal of Clinical Chemistry·Darryl EylesJohn McGrath
Jun 6, 2009·Journal of Computational Chemistry·Francesco AquilanteRoland Lindh
Sep 5, 2009·Accounts of Chemical Research·Orlando Acevedo, William L Jorgensen
Jan 14, 2010·Journal of the American Chemical Society·Hitoshi BanCarlos F Barbas
Apr 12, 2012·Physical Chemistry Chemical Physics : PCCP·Nicolas ChéronPaul Fleurat-Lessard
May 30, 2013·Bioconjugate Chemistry·Dennis M BauerLjiljana Fruk
Sep 23, 2014·Chemistry & Biology·Craig S McKay, M G Finn
Feb 24, 2015·Chemical Reviews·Omar Boutureira, Gonçalo J L Bernardes
Sep 12, 2015·ACS Chemical Biology·Shinichi SatoHiroyuki Nakamura
Jan 23, 2016·Chemical Society Reviews·Qi-Ying HuRoberto Adamo
Feb 24, 2016·Chemical Reviews·Kevin De BruyckerFilip E Du Prez
Apr 10, 2016·Journal of Computational Chemistry·Charlotte Brückner, Bernd Engels
Jun 1, 2017·Angewandte Chemie·Anu NaikNathan W Luedtke
Jul 17, 2018·Chemical Science·Maria Elena Ortiz-SotoJürgen Seibel

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Citations

Jun 3, 2020·Protein Science : a Publication of the Protein Society·Mahta MoinpourJacob C Schwartz
Jun 17, 2020·Chemistry : a European Journal·Dimitri Alvarez DortaSébastien G Gouin
Jan 30, 2021·Protein and Peptide Letters·Arnab ChowdhuryAnupam Bandyopadhyay

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